【作者】 张晔；

【导师】 王任直；

【作者基本信息】 北京协和医学院 ， 临床医学， 2009， 博士

【摘要】 目的了解ACTH腺瘤所致的Cushing病患者经蝶手术后复发相关的临床因素,寻找其中能较好预测术后复发的临床指标。通过免疫组化比较增殖性及侵袭性指标在复发组及非复发组内表达差异性,寻找导致复发的肿瘤细胞学特性及分子表型,为进一步探讨机制提供理论依据。方法在1990至2004间全部我院经蝶手术地库欣病患者中,随机选择诊断明确,入院前未接受过与库欣病相关的手术,术后经病理证实为垂体ACTH腺瘤且病历及随访资料完整的60例患者。依相应标准,分为复发及非复发组。回顾性分析组间性别、发病年龄、病程、肿瘤平均径线、术前及术后内分泌水平及手术情况等临床因素,同时运用免疫组化技术,分析Ki-67,基质金属蛋白酶9、垂体腺瘤转化基因及高迁移率蛋白A2在两组腺瘤组织中表达水平的差异。结果临床因素方面,较多的术中出血(通常>400ml)及术后血F值偏高可以作为库欣病经蝶手术后复发的较为可靠的预测因素,以术后一周早上8点血F值3.65ug/dl作为界值此判断术后复发的敏感性为75%,特异性为66.7%。此外,女性,术前影像学不明确和垂体平均径线大于等于1cm可能也是复发危险因素之一。四个侵袭及增殖指标中,基质金属蛋白酶9在复发组中表达显著增高(P=0.022),且表达量与复发间隔有极显著相关性(P=0.007,相关系数=-0.354),其余指标在两组间表达均无差异。结论垂体ACTH腺瘤经蝶术后复发是个多因素影响的过程。其中术中减少不必要的出血有助于减少复发,术后血皮质醇水平偏高预示术后可能复发。高表达基质金属蛋白酶9的垂体ACTH腺瘤具有较高的侵袭性,术中难以完全切净致使这部分肿瘤更易复发,且复发间隔时间较短。对于有复发高危因素的患者应密切随访。更多还原

【Abstract】 Objective To investigate the recurrence-related clinical factors in patients with adrenocorticotropic pituitary adenoma-induced Cushing’s disease who underwent transsphenoidal surgery and to find out the most predictive one(s) among them. We compared the expressions of several proliferative and invasive biomarkers by Immunohistochemistry to find out the recurrence-related cellular characteristic and molecular phenotype, which facilitates exploring its underlying mechanism.Method We randomly reviewed60patients with definite-diagnosed Cushing’s disease who had confirmed adrenocorticotropic pituitary adenoma after transsphenoidal surgery from1990to2004in our hospital. All of them didn’t receive any relevant treatment before admission and had long-term follow-up. They were assigned to recurrence or non-recurrence group according to relevant standards. We retrospectively analysed the gender, age, course, mean diameter of tumor, preoperative and postoperative hormone levels and the conditions during surgery. Meanwhile, we mensurated the different expressions of Ki-67, matrix metalloproteinase9, pituitary tumor transforming gene and high mobility group AT-hook2by Immunohistochemistry in two groups.Result Among clinical factors, high-volume blood loss during surgery (generally>400ml) and high postoperative cortisol level were most predictive indices. The postoperative cortisol level over3.65ug/dl predict recurrence with75%sensitivity and66.7%specificity. Moreover, female, mean diameter larger or equal to1cm and ambiguous preoperative MRI also seemed to be related to recurrence. The expression of matrix metalloproteinase9was significantly high in recurrence group (P=0.022) and was strongly related to the interval of recurrence (P=0.007, CC=-0.354). The other three biomarkers showed no statistic difference in two groups.Conclusion The recurrence of adrenocorticotropic pituitary adenoma after transsphenoidal surgery was influenced by multiple factors. Minimize the blood loss during surgery probably prevent recurrence. High postoperative cortisol level probably predicts recurrence. Tumors with high expression of matrix metalloproteinase9were more invasive, which means more difficult to be cut off completely. They were vulnerable to recurrence with shorter disease-free interval. The patients who had related risk factors should be followed-up closely.更多还原